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Cell Contact-Dependent Priming and Fc Interaction with CD32+ Immune Cells Contribute to the TGN1412-Triggered Cytokine Response.
- Source :
-
Journal of Immunology . 3/1/2014, Vol. 192 Issue 5, p2091-2098. 8p. - Publication Year :
- 2014
-
Abstract
- Following inconspicuous preclinical testing, the superagonistic anti-CD28 mAb TGN1412 was applied to six study participants who all developed a devastating cytokine storm.We verified that TGN1412 treatment of fresh PBMCs induced only moderate responses, whereas restoration of tissue-like conditions by high-density preculture (HDC) allowed vigorous cytokine production. TGN1412 treatment of T cells isolated from HDC-PBMCs induced moderate cytokine responses, which upon additional anti-IgG crosslinking were significantly boosted. Moreover, coincubation of TGN1412-treated T cells with B cells expressing the intermediate affinity Fcγ receptor IIB (CD32B), or coincubation with CD32B+ transfectants, resulted in robust T cell activation. This was surprising because TGN1412 was expressed as an Ig of the subclass 4 (IgG4), which was shown before to exhibit only minor affinity to FcγRs. Transcriptome analysis of TGN1412-treated T cells revealed that similar gene signatures were induced irrespective of whether T cells derived from fresh or HDC-PBMCs were studied. Collectively, these data indicate that HDC-PBMCs and HDC-PBMC- derived T cells mount rapid TGN1412 responses, which are massively boosted by FcγR crosslinking, in particular by CD32- expressing B cells. These results qualify HDC-PBMCs as a valuable in vitro test system for the analysis of complex mAb functions. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00221767
- Volume :
- 192
- Issue :
- 5
- Database :
- Academic Search Index
- Journal :
- Journal of Immunology
- Publication Type :
- Academic Journal
- Accession number :
- 103534964
- Full Text :
- https://doi.org/10.4049/jimmunol.1302461